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Developmental Endocrinology Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA
1Correspondence: Developmental Endocrinology Branch, NICHD, NIH, Bldg. 10, Rm. 10N262, 10 Center Dr. 1862, Bethesda, MD 20892, USA. E-mail: bondyc{at}exchange.nih.gov
Longitudinal bone growth, and hence stature, are functions of growth plate chondrocyte proliferation and hypertrophy. Insulin-like growth factor 1 (Igf1) is reputed to augment longitudinal bone growth by stimulating growth plate chondrocyte proliferation. In this study, however, we demonstrate that chondrocyte numbers and proliferation are normal in Igf1 null mice despite a 35% reduction in the rate of long bone growth. Igf1 null hypertrophic chondrocytes differentiate normally in terms of expressing specialized proteins such as collagen X and alkaline phosphatase, but are smaller than wild-type at all levels of the hypertrophic zone. The terminal hypertrophic chondrocytes, which form the scaffold on which long bone growth extends, are reduced in linear dimension by 30% in Igf1 null mice, accounting for most of their decreased longitudinal growth. The expression of the insulin-sensitive glucose transporter, GLUT4, is significantly decreased and the insulin-regulated enzyme glycogen synthase kinase 3ß (GSK3) is hypo-phosphorylated in Igf1 null chondrocytes. Glycogen levels were significantly decreased and ribosomal RNA levels were reduced by almost 75% in Igf1 null chondrocytes. These data suggest that Igf1 promotes longitudinal bone growth by `insulin-like' anabolic actions which augment chondrocyte hypertrophy.—Wang, J., Zhou, J., Bondy, C. A. Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy.
Key Words: glucose transporter • IGF action • insulin • proliferation • epiphysis • short stature
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